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Gene therapy cures male infertility

Male infertility has been cured with gene therapy for the first time. Although the breakthrough is in mice, the researchers think it will eventually lead to treatments for men.

“This is the beginning of a new era for infertility treatment,” says Takashi Shinohara, head of the team that cured the mice at Kyoto University.

Shinohara’s team successfully corrected a defective gene in Sertoli cells, which help sperm to mature. These specialised cells line ducts in the testes. They nourish immature germ cells and produce chemical cues that tell them to divide.

The mice were genetically engineered to have a defective version of a gene called Steel. When working properly, this gene produces a protein that enables Sertoli cells to swap messages with germ cells.

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Shinohara’s team used an adenovirus to ferry a correct version of Steel into the mice. Although the treated infertile males did not produce enough sperm to mate naturally, the investigators fertilised female mice through IVF after extracting semi-matured sperm from the testes of the males. These females gave birth to 13 females and seven healthy, fertile males.

Vanishing virus

The virus vanished after delivering the correct gene, raising hopes that it would not cause any immunological or genetic side-effects if used in men.

“If they’ve shown that, it’s very good,” says Robin Lovell-Badge, an expert in sperm development at the National Institute of Medical Research in London. “If you were ever going to do it in humans, you would have to know that the germ line would not be contaminated with virus at all,” he says.

Shinohara admits that even if the procedure is safe, it would be useless in men because they do not have the same gene mutation as the mice.

But defective Sertoli cells are to blame for 1 in 10 cases of male infertility. “Genes responsible for this are currently unknown, and I think it is likely some cases are caused by genes expressed in Sertoli cells just like the mutant mice we used for the experiment,” says Shinohara.

Lovell-Badge agrees. “It’s feasible there are mutations that affect humans as well,” he says.

He says that by tweaking the gene therapy procedure in mice, it should be possible to learn much more about how Sertoli cells and sperm interact.